Several neurotransmitter systems, including dopamine, serotonin, and glutamate, have been implicated in the etiology of schizophrenia and Tourette’s Syndrome, suggesting that a downstream mechanism common to each of these neurotransmitters may ultimately underlie these psychiatric disorders. We have developed mice in which the tetracycline system drives overexpression (within postnatal forebrain neurons) of the G-protein subunit Gαs, which couples receptors to stimulation of the cAMP cascade. Gαs mice show increased cAMP levels in striatum, but decreased cAMP in cortex and hippocampus. Gαs mice also exhibit enlarged ventricles (see MF Esposito et al., 2005, SFN abstract). Behaviorally, Gαs mice exhibit intact procedural learning but reduced sensorimotor gating, impaired hippocampus-dependent learning/memory, and hyperlocomotion. Importantly, cAMP and behavioral deficits of these mice reverse with suppression of transgene expression by doxycycline. Further, the phosphodiesterase inhibitor rolipram (0.66 mg/...